HCSGD entry for PML
1. General information
| Official gene symbol | PML |
|---|---|
| Entrez ID | 5371 |
| Gene full name | promyelocytic leukemia |
| Other gene symbols | MYL PP8675 RNF71 TRIM19 |
| Links to Entrez Gene | Links to Entrez Gene |
2. Neighbors in the network
3. Gene ontology annotation
GO ID | GO term | Evidence | Category |
|---|---|---|---|
| GO:0001666 | Response to hypoxia | IDA | biological_process |
| GO:0001932 | Regulation of protein phosphorylation | ISS | biological_process |
| GO:0002230 | Positive regulation of defense response to virus by host | IMP | biological_process |
| GO:0003677 | DNA binding | IEA | molecular_function |
| GO:0003713 | Transcription coactivator activity | IDA | molecular_function |
| GO:0005515 | Protein binding | IPI | molecular_function |
| GO:0005622 | Intracellular | IEA | cellular_component |
| GO:0005634 | Nucleus | IDA | cellular_component |
| GO:0005654 | Nucleoplasm | IDA TAS | cellular_component |
| GO:0005730 | Nucleolus | IDA | cellular_component |
| GO:0005737 | Cytoplasm | IDA | cellular_component |
| GO:0005829 | Cytosol | ISS | cellular_component |
| GO:0006351 | Transcription, DNA-templated | IEA | biological_process |
| GO:0006355 | Regulation of transcription, DNA-templated | IMP | biological_process |
| GO:0006461 | Protein complex assembly | IDA | biological_process |
| GO:0006605 | Protein targeting | IDA IMP | biological_process |
| GO:0006915 | Apoptotic process | IDA | biological_process |
| GO:0006919 | Activation of cysteine-type endopeptidase activity involved in apoptotic process | IEA | biological_process |
| GO:0006977 | DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest | ISS | biological_process |
| GO:0007050 | Cell cycle arrest | IDA IEA | biological_process |
| GO:0007179 | Transforming growth factor beta receptor signaling pathway | IEA | biological_process |
| GO:0007182 | Common-partner SMAD protein phosphorylation | IEA | biological_process |
| GO:0007184 | SMAD protein import into nucleus | IEA | biological_process |
| GO:0008270 | Zinc ion binding | IDA IEA | molecular_function |
| GO:0008285 | Negative regulation of cell proliferation | IMP | biological_process |
| GO:0008630 | Intrinsic apoptotic signaling pathway in response to DNA damage | IDA | biological_process |
| GO:0008631 | Intrinsic apoptotic signaling pathway in response to oxidative stress | IEA | biological_process |
| GO:0009411 | Response to UV | IEA | biological_process |
| GO:0010332 | Response to gamma radiation | IEA | biological_process |
| GO:0010522 | Regulation of calcium ion transport into cytosol | ISS | biological_process |
| GO:0016032 | Viral process | IEA | biological_process |
| GO:0016363 | Nuclear matrix | IDA IEA | cellular_component |
| GO:0016525 | Negative regulation of angiogenesis | IMP | biological_process |
| GO:0016605 | PML body | IDA TAS | cellular_component |
| GO:0019221 | Cytokine-mediated signaling pathway | TAS | biological_process |
| GO:0030099 | Myeloid cell differentiation | IEA | biological_process |
| GO:0030308 | Negative regulation of cell growth | IDA | biological_process |
| GO:0030578 | PML body organization | IDA IMP | biological_process |
| GO:0031065 | Positive regulation of histone deacetylation | IDA | biological_process |
| GO:0031625 | Ubiquitin protein ligase binding | IPI | molecular_function |
| GO:0031901 | Early endosome membrane | IEA | cellular_component |
| GO:0031965 | Nuclear membrane | IDA | cellular_component |
| GO:0032183 | SUMO binding | IPI | molecular_function |
| GO:0032211 | Negative regulation of telomere maintenance via telomerase | IMP | biological_process |
| GO:0032469 | Endoplasmic reticulum calcium ion homeostasis | ISS | biological_process |
| GO:0032938 | Negative regulation of translation in response to oxidative stress | IDA | biological_process |
| GO:0034097 | Response to cytokine | IDA | biological_process |
| GO:0042406 | Extrinsic component of endoplasmic reticulum membrane | ISS | cellular_component |
| GO:0042771 | Intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator | ISS | biological_process |
| GO:0042803 | Protein homodimerization activity | IPI | molecular_function |
| GO:0043161 | Proteasome-mediated ubiquitin-dependent protein catabolic process | IDA | biological_process |
| GO:0045165 | Cell fate commitment | IEA | biological_process |
| GO:0045343 | Regulation of MHC class I biosynthetic process | IEA | biological_process |
| GO:0045892 | Negative regulation of transcription, DNA-templated | IDA | biological_process |
| GO:0045930 | Negative regulation of mitotic cell cycle | IDA | biological_process |
| GO:0046332 | SMAD binding | IEA | molecular_function |
| GO:0046982 | Protein heterodimerization activity | IDA | molecular_function |
| GO:0048384 | Retinoic acid receptor signaling pathway | IEA | biological_process |
| GO:0050821 | Protein stabilization | IDA | biological_process |
| GO:0050897 | Cobalt ion binding | IDA | molecular_function |
| GO:0051457 | Maintenance of protein location in nucleus | IDA | biological_process |
| GO:0051607 | Defense response to virus | IEA | biological_process |
| GO:0051974 | Negative regulation of telomerase activity | IMP | biological_process |
| GO:0060058 | Positive regulation of apoptotic process involved in mammary gland involution | IDA | biological_process |
| GO:0060333 | Interferon-gamma-mediated signaling pathway | TAS | biological_process |
| GO:0060444 | Branching involved in mammary gland duct morphogenesis | IEA | biological_process |
| GO:0070059 | Intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress | IEA | biological_process |
| GO:0071353 | Cellular response to interleukin-4 | IEA | biological_process |
| GO:0090398 | Cellular senescence | IDA | biological_process |
| GO:0097191 | Extrinsic apoptotic signaling pathway | IEA | biological_process |
| GO:2000059 | Negative regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process | IMP | biological_process |
| GO:2000779 | Regulation of double-strand break repair | IMP | biological_process |
| GO:2001238 | Positive regulation of extrinsic apoptotic signaling pathway | IMP | biological_process |
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4. Expression levels in datasets
- Meta-analysis result
| p-value up | p-value down | FDR up | FDR down |
|---|---|---|---|
| 0.0245481935 | 0.9912136545 | 0.3698202626 | 1.0000000000 |
- Individual experiment result
( "-" represent NA in the specific microarray platform )
( "-" represent NA in the specific microarray platform )
| Data source | Up or down | Log fold change |
|---|---|---|
| GSE11954 | Up | 0.0636691697 |
| GSE13712_SHEAR | Up | 0.3666421673 |
| GSE13712_STATIC | Up | 0.6069737799 |
| GSE19018 | Up | 0.0843784623 |
| GSE19899_A1 | Down | -0.0180461354 |
| GSE19899_A2 | Up | 0.1706160984 |
| PubMed_21979375_A1 | Down | -0.0305152231 |
| PubMed_21979375_A2 | Up | 0.3922337598 |
| GSE35957 | Up | 0.2373143562 |
| GSE36640 | Up | 0.2594793291 |
| GSE54402 | Up | 0.0138991405 |
| GSE9593 | Up | 0.4694532187 |
| GSE43922 | Up | 0.0502597821 |
| GSE24585 | Up | 0.4308619249 |
| GSE37065 | Up | 0.2369869308 |
| GSE28863_A1 | Up | 0.3008038629 |
| GSE28863_A2 | Up | 0.6789176220 |
| GSE28863_A3 | Up | 0.1156913010 |
| GSE28863_A4 | Up | 0.1988150600 |
| GSE48662 | Up | 0.2269580287 |
5. Regulation relationships with compounds/drugs/microRNAs
- Compounds
Not regulated by compounds
- Drugs
Not regulated by drugs
- MicroRNAs
- mirTarBase
- mirTarBase
MiRNA_name | mirBase ID | miRTarBase ID | Experiment | Support type | References (Pubmed ID) |
|---|---|---|---|---|---|
| hsa-miR-335-5p | MIMAT0000765 | MIRT018318 | Microarray | Functional MTI (Weak) | 18185580 |
| hsa-miR-423-3p | MIMAT0001340 | MIRT042535 | CLASH | Functional MTI (Weak) | 23622248 |
| hsa-miR-378a-3p | MIMAT0000732 | MIRT043919 | CLASH | Functional MTI (Weak) | 23622248 |
Entries Per Page
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- mirRecord
No target information from mirRecord
- mirRecord
6. Text-mining results about the gene
Gene occurances in abstracts of cellular senescence-associated articles: 70 abstracts the gene occurs.
PubMed ID of the article | Sentenece the gene occurs |
|---|---|
| 27206849 | Promyelocytic leukemia (PML) plays a tumor suppressive role by inducing cellular senescence in response to oncogenic stress |
| 27206849 | However, tumor cell lines fail to engage in complete senescence upon PML activation |
| 27206849 | Here, we report that activation of the cyclin-dependent kinases CDK4 and CDK6 are essential and sufficient to impair senescence induced by PML expression |
| 26529363 | Moreover, c-Myc downregulation was partially mediated by proteasome-dependent degradation within promyelocytic leukemia (PML) nuclear bodies, which were found to be highly abundant during RAD21 knockdown-induced senescence |
| 26119943 | PML is required for telomere stability in non-neoplastic human cells |
| 26119943 | In tumors, telomere length is maintained by Telomerase activity or by the Alternative Lengthening of Telomeres mechanism, whose hallmark is the telomeric localization of the promyelocytic leukemia (PML) protein |
| 26119943 | Whether PML contributes to telomeres maintenance in normal cells is unknown |
| 26119943 | We show that in normal human fibroblasts the PML protein associates with few telomeres, preferentially when they are damaged |
| 26119943 | Proliferation-induced telomere attrition or their damage due to alteration of the shelterin complex enhances the telomeric localization of PML, which is increased in human T-lymphocytes derived from patients genetically deficient in telomerase |
| 26119943 | In normal fibroblasts, PML depletion induces telomere damage, nuclear and chromosomal abnormalities, and senescence |
| 26119943 | Expression of the leukemia protein PML/RARalpha in hematopoietic progenitors displaces PML from telomeres and induces telomere shortening in the bone marrow of pre-leukemic mice |
| 26119943 | Our work provides a novel view of the physiologic function of PML, which participates in telomeres surveillance in normal cells |
| 26119943 | Our data further imply that a diminished PML function may contribute to cell senescence, genomic instability, and tumorigenesis |
| 26085373 | CK2 upregulation in Pten null tumours affects the stability of Pml, an essential regulator of senescence |
| 26085373 | However, CK2 inhibition stabilizes Pml levels enhancing senescence in Pten null tumours |
| 25815425 | Intrinsically aged NHDFs in culture exhibited more frequently nuclear foci positive for p53 binding protein 1 and promyelocytic leukemia protein reminiscent of 'DNA segments with chromatin alterations reinforcing senescence (DNA-SCARS)' |
| 25744025 | We show both prelamin A accumulation and increased DNA damage occur concomitantly, before VSMC replicative senescence, and induce the localisation of ERK1/2 to promyelocytic leukaemia protein nuclear bodies (PML NBs) at the sites of DNA damage via nesprin-2 and lamin A interactions |
| 25744025 | Importantly, VSMCs treated with DNA damaging agents also displayed prelamin A accumulation and ERK compartmentalisation at PML NBs, suggesting that prelamin A and nesprin-2 are novel components of the DDR |
| 25744025 | In support of this, disruption of ERK compartmentalisation at PML NBs, by either depletion of nesprin-2 or lamins A/C, resulted in the loss of ATM from DNA lesions |
| 25744025 | We conclude that lamins A/C and PML act as scaffolds to organise DNA-repair foci and compartmentalise nesprin-2/ERK signalling |
| 25744025 | However, nesprin-2/ERK signalling fidelity, but not their compartmentalisation at PML NBs, is essential for efficient DDR in VSMCs |
| 25354534 | The key role of PML in IFN-alpha induced cellular senescence of human mesenchymal stromal cells |
| 25354534 | The recombinant lentiviral vector, which encodes shRNA against PML or full-length PML cDNA, was constructed |
| 25354534 | By knocking-down and overexpressing PML, we found that PML was indispensable to IFN-alpha mediated hMSC senescence |
| 25092303 | Although expression of the human PML fusion in mice promotes leukemia, its efficiency is rather low |
| 25092303 | Unexpectedly, we find that simply replacing the human PML fusion with its mouse counterpart results in a murine PML-RARalpha (mPR) hybrid protein that is transformed into a significantly more leukemogenic oncoprotein |
| 24838245 | Calpain 5 is highly expressed in the central nervous system (CNS), carries dual nuclear localization signals, and is associated with nuclear promyelocytic leukemia protein bodies |
| 24838245 | Interestingly, CAPN5 is found in punctate domains associated with promyelocytic leukemia (PML) protein within the nucleus |
| 24838245 | PML nuclear bodies are implicated in transcriptional regulation, cell differentiation, cellular response to stress, viral defense, apoptosis, and cell senescence as well as protein sequestration, modification, and degradation |
| 24615016 | The tumor suppressor PML specifically accumulates at RPA/Rad51-containing DNA damage repair foci but is nonessential for DNA damage-induced fibroblast senescence |
| 24615016 | The PML tumor suppressor has been functionally implicated in DNA damage response and cellular senescence |
| 24615016 | Direct evidence for such a role based on PML knockdown or knockout approaches is still lacking |
| 24615016 | We have therefore analyzed the irradiation-induced DNA damage response and cellular senescence in human and mouse fibroblasts lacking PML |
| 24615016 | Our data show that PML nuclear bodies (NBs) nonrandomly associate with persistent DNA damage foci in unperturbed human skin and in high-dose-irradiated cell culture systems |
| 24615016 | PML bodies do not associate with transient gammaH2AX foci after low-dose gamma irradiation |
| 24615016 | Superresolution microscopy reveals that all PML bodies within a nucleus are engaged at Rad51- and RPA-containing repair foci during ongoing DNA repair |
| 24615016 | The lack of PML (i) does not majorly affect the DNA damage response, (ii) does not alter the efficiency of senescence induction after DNA damage, and (iii) does not affect the proliferative potential of primary mouse embryonic fibroblasts during serial passaging |
| 24615016 | Thus, while PML NBs specifically accumulate at Rad51/RPA-containing lesions and senescence-derived persistent DNA damage foci, they are not essential for DNA damage-induced and replicative senescence of human and murine fibroblasts |
| 24351540 | The retinoblastoma protein and PML collaborate to organize heterochromatin and silence E2F-responsive genes during senescence |
| 24351540 | We report that in mouse embryonic fibroblasts, endogenous promyelocytic leukemia protein (PML) associates with E2F target genes in a pRB LXCXE-dependent manner during HrasV12-induced senescence |
| 24351540 | Furthermore, using a PML-IV-induced senescence model, we show that the pRB LXCXE binding cleft is essential for PML association with gene promoters, silencing of E2F target genes, and stable cell cycle exit |
| 24351540 | Binding assays show that pRB can interact with PML specifically during senescence, suggesting that signaling events in senescence regulate assembly of PML and pRB to establish heterochromatin and create a permanent cell cycle arrest |
| 24200965 | 3 from pericentromeric heterochromatin upon DAXX or PML depletion suggests that the targeting of H3 |
| 23935871 | In this study, we found that MCAF1 localizes to PML nuclear bodies in human fibroblasts and non-cancerous cells |
| 23935871 | Consistently, in activated Ras-induced senescent fibroblasts, the accumulation of MCAF1 in PML bodies was enhanced via the binding of this protein to SUMO molecules, suggesting that sequestration of MCAF1 to PML bodies promotes cellular senescence |
| 23933816 | ATM kinase enables the functional axis of YAP, PML and p53 to ameliorate loss of Werner protein-mediated oncogenic senescence |
| 23933816 | YAP upregulation correlates with slower cell proliferation and accelerated senescence, which are partially mediated by the formation of a complex between YAP and the PML protein, whose activity promotes p53 activation |
| 23933816 | The ATM kinase is necessary for YAP and PML accumulation in WRN-depleted cells |
| 23933816 | Notably, the depletion of either YAP or PML partially impairs the induction of senescence following WRN loss |
| 23933816 | The latter has features of SASP (senescence-associated secretory phenotype), whose protumorigenic properties are potentiated by YAP, PML and p53 depletion |
| 23656786 | Loss of PML cooperates with mutant p53 to drive more aggressive cancers in a gender-dependent manner |
| 23656786 | UNLABELLED: p53 mutations and downregulation of promyelocytic leukemia (PML) are common genetic alterations in human cancers |
| 23656786 | The contribution of PML to mutant p53 driven cancer was evaluated in a mouse model harboring a p53 mutation (p53 (wild-type/R172H) ) that recapitulates a frequent p53 mutation (p53 (R175H) ) in human sporadic and Li-Fraumeni cancers |
| 23656786 | These mice with PML displayed perturbation of the hematopoietic compartment, manifested either as lymphoma or extramedullary hematopoiesis (EMH) |
| 23656786 | In contrast, a complete loss of PML from these mice resulted in a marked alteration in tumor profile |
| 23656786 | Further, males lacking PML exhibited a high incidence of soft tissue sarcomas and reduced survival, while females largely developed osteosarcomas, without impact on survival |
| 23656786 | Together, these findings demonstrate that PML is an important tumor suppressor dictating disease development in a pertinent mouse model of human cancer |
| 23486996 | Compound In Vivo Inactivation of Pml and p53 Uncovers a Functional Interaction in Angiosarcoma Suppression |
| 23486996 | The promyelocytic leukemia (PML) tumor suppressor gene was initially identified as part of the t(15:17) chromosomal translocation associated with acute promyelocytic leukemia (APL) |
| 23486996 | The PML protein is responsible for the assembly and function of characteristic nuclear domains known as PML-nuclear bodies (PML-NBs), which have been implicated in a variety of cellular functions, including growth suppression, apoptosis, and cellular senescence |
| 23486996 | It has been shown that PML favors both p53 accumulation and transcriptional activity; in turn, PML expression is directly regulated by p53, and this reciprocal regulation contributes to p53-mediated apoptosis and senescence |
| 23486996 | Here we show that complete Pml inactivation, in a context of p53 heterozygosity, redistributes and expands the tumor spectrum leading to the formation of angiosarcomas and increased lymphomagenesis |
| 23486996 | Importantly, we find that Pml inactivation decreases the rate of loss of heterozygosity (LOH) in the remaining p53 allele, revealing the relevancy of p53 haploinsufficiency to tumorigenesis |
| 22904064 | PRMT6(-/-) MEFs displayed high transcriptional levels of p53 and its targets, p21 and PML |
| 22829758 | These include COL4A3, CFLAR, GULP1, PDCD1, CASP10, PAX3, BOK, HSPD1, PITX2, and PML |
| 22778276 | The cell biology of disease: Acute promyelocytic leukemia, arsenic, and PML bodies |
| 22778276 | Acute promyelocytic leukemia (APL) is driven by a chromosomal translocation whose product, the PML/retinoic acid (RA) receptor alpha (RARA) fusion protein, affects both nuclear receptor signaling and PML body assembly |
| 22778276 | Dissection of APL pathogenesis has led to the rediscovery of PML bodies and revealed their role in cell senescence, disease pathogenesis, and responsiveness to treatment |
| 22778276 | APL is remarkable because of the fortuitous identification of two clinically effective therapies, RA and arsenic, both of which degrade PML/RARA oncoprotein and, together, cure APL |
| 22778276 | Analysis of arsenic-induced PML or PML/RARA degradation has implicated oxidative stress in the biogenesis of nuclear bodies and SUMO in their degradation |
| 22737272 | The results also indicate that levels of the tumor suppressor protein PML are higher in the active regions of keloid |
| 22689861 | B-cell lymphomas deficient for E6AP expressed elevated levels of PML and PML-nuclear bodies with a concomitant increase in markers of cellular senescence, including p21, H3K9me3, and p16 |
| 22689861 | Consistently, PML deficiency accelerated the rate of Myc-induced B-cell lymphomagenesis |
| 22689861 | Importantly, E6AP expression was elevated in approximately 60% of human Burkitt lymphomas, and down-regulation of E6AP in B-lymphoma cells restored PML expression with a concurrent induction of cellular senescence in these cells |
| 22689861 | This provides a molecular explanation for the down-regulation of PML observed in non-Hodgkin lymphomas, thereby suggesting a novel therapeutic approach for restoration of tumor suppression in B-cell lymphoma |
| 22641694 | TERRA foci did not colocalize with gammaH2AX foci, promyelocytic leukemia (PML) or Cajal bodies in mouse tumor tissue |
| 22615843 | IFN-beta appears to induce senescence by upregulating the expression of the tumor suppressor PML, a well known IFN-induced gene |
| 22615843 | Indeed, experiments in gene silencing via specific siRNAs have shown that PML is essential in the execution of the senescence programme and that both p53 and p21 pathways are involved |
| 22513787 | Specifically, we analyzed effectors of senescence, including p16(INK4a), p53, and DNA damage (gamma-H2AX), as well as predictive markers of senescence including Ki67, PML, senescence-associated beta-galactosidase, heterochromatic foci (H3K9Me, 4'-6-diamidino-2-phenylindole), and nuclear size |
| 22403609 | The two pathways engaged in a cross-talk, likely via PML tumor suppressor, whose localization to senescence-associated chromatin foci was increased by AR activation |
| 22359342 | Translation-dependent mechanisms lead to PML upregulation and mediate oncogenic K-RAS-induced cellular senescence |
| 22359342 | The PML tumour suppressor was initially identified as a component of the PML-RARalpha oncoprotein of acute promyelocytic leukaemia (APL) |
| 22359342 | PML, a critical OIS mediator, is upregulated by oncogenic K-RAS in vivo and in vitro |
| 22359342 | We demonstrate here that oncogenic K-RAS induces PML protein upregulation by activating the RAS/MEK1/mTOR/eIF4E pathway even in the absence of p53 |
| 22359342 | Under these circumstances, PML mRNA is selectively associated to polysomes |
| 22359342 | Importantly, we find that the PML 5' untranslated mRNA region plays a key role in mediating PML protein upregulation and that its presence is essential for an efficient OIS response |
| 22359342 | These findings demonstrate that upregulation of PML translation plays a central role in oncogenic K-RAS-induced OIS |
| 22117195 | The promyelocytic leukemia (PML) tumor suppressor is a regulator of p53 acetylation and function in cellular senescence |
| 22117195 | Moreover, a fraction of MageA2 colocalizes with PML-NBs through direct association with PML, and decreases PMLIV sumoylation through an HDAC-dependent mechanism |
| 22117195 | This reduction in PML post-translational modification promotes defects in PML-NBs formation |
| 22117195 | All these data suggest that MageA2, in addition to its anti-apoptotic effect, could have a novel role in the early progression to malignancy by interfering with PML/p53 function, thereby blocking the senescence program, a critical barrier against cell transformation |
| 22110753 | METHODOLOGY/PRINCIPAL FINDINGS: In this study, by using a dominant negative mutant human telomerase reverse transcriptase (hTERT) vector to inhibit TA in bladder cancer T24 cells, we observed the appearance of long phenotype of telomere length and the ALT-associated PML body (APB) complex after the 27(th) passage, indicating the occurrence of ALT-like pathway in surviving T24/DN868A cells with telomerase inhibition |
| 22010578 | E2FBP1 antagonizes the p16(INK4A)-Rb tumor suppressor machinery for growth suppression and cellular senescence by regulating promyelocytic leukemia protein stability |
| 22010578 | Cellular senescence is an irreversible cell cycle arrest triggered by the activation of oncogenes or mitogenic signaling as well as the enforced expression of tumor suppressors such as p53, p16(INK4A) and promyelocytic leukemia protein (PML) in normal cells |
| 22010578 | E2F-binding protein 1 (E2FBP1), a transcription regulator for E2F, induces PML reduction and suppresses the formation of PML-nuclear bodies, whereas the down-regulation of E2FBP1 provokes the PML-dependent premature senescence in human normal fibroblasts |
| 22010578 | Here we report that the depletion of E2FBP1 induces the accumulation of PML through the Ras-dependent activation of MAP kinase signaling |
| 22010578 | These results suggest that E2FBP1 functions as a critical antagonist to the p16(INK4A)-Rb tumor suppressor machinery by regulating PML stability |
| 22002537 | Physical and functional interaction between PML and TBX2 in the establishment of cellular senescence |
| 22002537 | Previous studies showed that the PML tumour suppressor promotes senescence, although the precise mechanisms remain to be elucidated |
| 22002537 | Recruitment of PML to the TBX2 promoter is dependent on a functional p130/E2F4 repressor complex ultimately implementing a transcriptionally inactive chromatin environment at the TBX2 promoter |
| 22002537 | TBX2 repression actively contributes to senescence induction as cells depleted for TBX2 trigger PML pro-senescence function(s) and enter senescence |
| 22002537 | Reciprocally, elevated TBX2 levels antagonize PML pro-senescence function through direct protein-protein interaction |
| 22002537 | Collectively, our findings indicate that PML and TBX2 act in an autoregulatory loop to control the effective execution of the senescence program |
| 21779477 | A Role for PML in Innate Immunity |
| 21779477 | The promyelocytic leukemia gene (PML) of acute promyelocytic leukemia is an established tumor suppressor gene with critical functions in growth suppression, induction of apoptosis, and cellular senescence |
| 21779477 | Interestingly, although less studied, PML seems to play a key role also in immune response to viral infection |
| 21779477 | Herein, we report that Pml(-/-) mice spontaneously develop an atypical invasive and lethal granulomatous lesion known as botryomycosis (BTM) |
| 21779477 | In Pml(-/-) mice, BTM is the result of impaired function of macrophages, whereby they fail to become activated and are thus unable to clear pathogenic microorganisms |
| 21779477 | Accordingly, Pml(-/-) mice are resistant to lipopolysaccharide (LPS)-induced septic shock as a result of an ineffective production of cytokines and chemokines, suggesting a role for PML in the innate immune Toll-like receptor (TLR)/NF-kappaB prosurvival pathway |
| 21779477 | These results not only shed light on a new fundamental function of PML in innate immunity, but they also point to a proto-oncogenic role for PML in certain cellular and pathological contexts |
| 21228624 | The promyelocytic leukemia (PML) protein is the main structural component of subnuclear domains termed PML nuclear bodies (PML NBs), which are implicated in tumor suppression by regulating apoptosis, cell senescence, and DNA repair |
| 21228624 | Previously, we demonstrated that ATM kinase can regulate changes in PML NB number in response to DNA double-strand breaks (DSBs) |
| 21228624 | This increase in PML NB number correlated with decreased nuclear lamina-associated heterochromatin and a 30% reduction in chromatin density as observed by electron microscopy, which is reminiscent of DNA damaged chromatin |
| 21228624 | These changes in chromatin ultrastructure also correlated with increased histone H4 acetylation, and treatment with the HDAC inhibitor TSA failed to further increase PML NB number |
| 21228624 | Together these data implicate KAP1-dependent changes in chromatin structure as one possible mechanism by which ATM may regulate PML NB number in response to DNA damage |
| 21205865 | Regulation of E2Fs and senescence by PML nuclear bodies |
| 21205865 | The tumor suppressor PML (promyelocytic leukemia protein) regulates cellular senescence and terminal differentiation, two processes that implicate a permanent exit from the cell cycle |
| 21205865 | Here, we show that the mechanism by which PML induces a permanent cell cycle exit and activates p53 and senescence involves a recruitment of E2F transcription factors bound to their promoters and the retinoblastoma (Rb) proteins to PML nuclear bodies enriched in heterochromatin proteins and protein phosphatase 1alpha |
| 21205865 | In benign prostatic hyperplasia, a neoplastic disease that displays features of senescence, PML was found to be up-regulated and forming nuclear bodies |
| 21205865 | In contrast, PML bodies were rarely visualized in prostate cancers |
| 21205865 | The newly defined PML/Rb/E2F pathway may help to distinguish benign tumors from cancers, and suggest E2F target genes as potential targets to induce senescence in human tumors |
| 21198351 | Role of promyelocytic leukemia protein in host antiviral defense |
| 21198351 | Several pathways have been implicated in the establishment of antiviral state in response to interferon (IFN), one of which implicates the promyelocytic leukemia (PML) protein |
| 21198351 | The PML gene has been discovered 20 years ago and has led to new insights into oncogenesis, apoptosis, cell senescence, and antiviral defense |
| 21198351 | PML is induced by IFN, leading to a marked increase of expression of PML isoforms and the number of PML nuclear bodies (NBs) |
| 21198351 | PML is the organizer of the NBs that contains at least 2 permanent NB-associated proteins, the IFN-stimulated gene product Speckled protein of 100 kDa (Sp100) and death-associated dead protein (Daxx), as well as numerous other transient proteins recruited in these structures in response to different stimuli |
| 21198351 | Accumulating reports have implicated PML in host antiviral defense and revealed various strategies developed by viruses to disrupt PML NBs |
| 21198351 | This review will focus on the regulation of PML and the implication of PML NBs in conferring resistance to DNA and RNA viruses |
| 21118958 | Unlike transient foci, DNA-SCARS associate with PML nuclear bodies, lack the DNA repair proteins RPA and RAD51, lack single-stranded DNA and DNA synthesis and accumulate activated forms of the DDR mediators CHK2 and p53 |
| 20946972 | The senescence phenotype is characterised by altered cellular morphology, increased activity for senescence-associated-beta-galactosidase (SA-beta-GAL), increased formation of senescence-associated heterochromatin foci (SAHF) and promyelocytic leukemia protein nuclear bodies (PML NBs), permanent DNA damage, chromosomal instability and an inflammatory secretome |
| 20841375 | 2 knockdown cells displayed increased levels of PML bodies, DNA damage (gammaH2AX) foci, senescence-associated heterochromatin foci, mitochondrial dysfunction, secretory phenotype, and phosphatase inactivation |
| 20699642 | Regulation of the PML tumor suppressor in drug-induced senescence of human normal and cancer cells by JAK/STAT-mediated signaling |
| 20699642 | The Promyelocytic leukemia protein (PML) tumor suppressor is upregulated in several forms of cellular senescence, however the mechanism of its induction is elusive |
| 20699642 | Chemical inhibition of all JAK kinases and RNAi-mediated knock-down of JAK1 suppressed PML expression, implicating JAK/STAT-mediated signaling in regulation of the PML gene |
| 20699642 | As PML protein stability remained unchanged after drug treatment, decreased protein turnover was unlikely to explain the senescence-associated increased abundance of PML |
| 20699642 | Furthermore, binding activity of Interferon Stimulated Response Element (ISRE) within the PML gene promoter, and suppression of reporter gene activity after deletion of ISRE from the PML promoter region suggested that drug-induced PML transcription is controlled via transcription factors interacting with this element |
| 20699642 | Collectively, our data show that upregulation of the PML tumor suppressor in cellular senescence triggered by diverse drugs including clinically used anti-cancer chemotherapeutics relies on stimulation of PML transcription by JAK/STAT-mediated signaling, possibly evoked by the autocrine/paracrine activities of senescence-associated cytokines |
| 20501696 | Two-step colocalization of MORC3 with PML nuclear bodies |
| 20501696 | Many functional subdomains, including promyelocytic leukemia nuclear bodies (PML NBs), are formed in the mammalian nucleus |
| 20501696 | Various proteins are constitutively or transiently accumulated in PML NBs in a PML-dependent manner |
| 20501696 | MORC3 (microrchidia family CW-type zinc-finger 3), also known as NXP2, which consists of GHL-ATPase, a CW-type zinc-finger and coiled-coil domains, is localized in PML NBs, where it recruits and activates p53 to induce cellular senescence |
| 20501696 | Here, we show that MORC3 colocalizes with PML by a two-step molecular mechanism: the PML-independent formation of MORC3 NDs by the ATPase cycle, and the association of MORC3 with PML via the SUMO1-SUMO-interacting motif (SIM) |
| 20501696 | Furthermore, the SUMOylation of MORC3 at five sites was involved in the association of MORC3 with PML, and SUMO1-unmodified MORC3 formed NDs independently of PML |
| 20457152 | IF analysis also showed that the ETC generate PML bodies that appear to concentrate OCT4, NANOG and SOX2 proteins, which extend into complex nuclear networks |
| 20069564 | Telomeres also co-localized with promyelocytic leukemia bodies (PML) |
| 19802007 | Here, we show that genotoxic drugs capable of inducing premature senescence in normal and cancer cells, such as 5-bromo-2'-deoxyuridine (BrdU), distamycin A (DMA), aphidicolin and hydroxyurea, persistently activate Janus kinase-signal transducer and activator of transcription (JAK/STAT) signaling and expression of interferon-stimulated genes (ISGs), such as MX1, OAS, ISG15, STAT1, PML, IRF1 and IRF7, in several human cancer cell lines |
| 19589617 | With cell passages, the 20S core protein progressively accumulated into discrete nuclear foci that largely colocalized with promyelocytic leukemia (PML) bodies while p21 accumulated throughout the nuclear compartment |
| 19273079 | PML links aberrant cytokine signaling and oncogenic stress to cellular senescence |
| 19273079 | Senescence is a tumor suppressor mechanism triggered by oncogenic stimuli and characterized by a permanent cell cycle arrest mediated by tumor suppressors such as p53, Rb and PML |
| 19273079 | PML itself is critical for the formation of nuclear bodies (PML bodies) that accumulate in senescent cells rendering them suitable markers for the senescence phenotype |
| 19273079 | The mechanism of PML-induction during senescence is complex and includes increased PML gene transcription by p53 or transcription factors of the interferon/Jak/Stat pathway |
| 19273079 | In turn, PML engages both p53 and Rb, although the precise molecular processes are unknown |
| 19273079 | PML interacts with the DNA-binding domain of p53 facilitating p53 modifications |
| 19273079 | PML can also interact with Rb and may play a role in Rb-dependent gene silencing during senescence |
| 19273079 | Recent studies suggest an additional connection between PML and the senescence program |
| 19273079 | Intriguingly, proteins that signal DNA damage or help repairing it localize to PML bodies, suggesting that PML may play a role in the DNA damage response during senescence |
| 19273079 | We think that the discovery of factors acting upstream or downstream PML may help to understand how cells bypass senescence on their way to tumorigenesis |
| 19273079 | More importantly the PML pathway may eventually lead to novel anti-cancer therapies |
| 18852884 | Further analysis suggested that promyolocytic leukemia protein (PML) bodies are dramatically increased in HFF-MBPsi-4 |
| 18566754 | CK2 mediates phosphorylation and ubiquitin-mediated degradation of the PML tumor suppressor |
| 18566754 | The PML tumor suppressor controls growth suppression, induction of apoptosis, and cellular senescence |
| 18566754 | PML loss occurs frequently in hematopoietic and solid tumors |
| 18566754 | PML loss often correlates with tumor progression |
| 18566754 | PML degradation depends on direct CK2 phosphorylation of PML Ser517 |
| 18566754 | PML mutants that are resistant to CK2 phosphorylation display increased tumor suppressive functions in assays measuring apoptosis, replicative senescence, and in xenograft models |
| 18566754 | More significantly, CK2 pharmacological inhibition enhances PML tumor suppressive property |
| 18566754 | These data identify a key post-translational mechanism that controls PML protein levels in cancer cells and suggest that CK2 inhibitors may be beneficial anti-cancer drugs |
| 18298799 | Modulation of M2-type pyruvate kinase activity by the cytoplasmic PML tumor suppressor protein |
| 18298799 | The promyelocytic leukemia (PML) tumor suppressor protein accumulates in PML nuclear bodies (PML-NBs), and can induce growth arrest, cellular senescence and apoptosis |
| 18298799 | PML has also been localized in the cytoplasm, although its function in this localization remains elusive |
| 18298799 | Here, we have shown that cytoplasmic PML (cPML) directly interacts with M2-type pyruvate kinase (PKM2), a key regulator of carbon fate |
| 18298799 | Over-expression of PML-2KA mutant in the cytoplasm, which was generated by mutagenesis of the nuclear localization signals of PML, in MCF-7 breast cancer cells suppressed PKM2 activity and the accumulation of lactate |
| 18203716 | Mammalian Sir2 (SIRT1) has also been found to regulate premature cellular senescence induced by the tumor suppressors PML and p53 |
| 18056407 | Alternative lengthening of telomere (ALT) tumors maintain telomeres by a telomerase-independent mechanism and are characterized by a nuclear structure called the ALT-associated PML body (APB) |
| 18056407 | In this context, PML is indispensable for p53-dependent p21 induction |
| 18031568 | We also found that promyelocytic leukemia protein and acetylated p53, key proteins involved in stress-induced premature senescence in proliferating cells, were associated with cellular alterations of senescence in DOX-treated cardiomyocytes |
| 17996922 | Expression and localization of Werner syndrome protein is modulated by SIRT1 and PML |
| 17996922 | Endogenous WRN and BLM proteins localize in nucleoli and in nuclear PML bodies defined by isoforms of the PML protein, which is a key regulator of cellular senescence |
| 17996922 | We identified PML isoforms associating with the nuclear bodies |
| 17878236 | A nucleolar targeting signal in PML-I addresses PML to nucleolar caps in stressed or senescent cells |
| 17878236 | The promyelocytic leukemia (PML) tumour suppressor is the organiser of PML nuclear bodies, which are domains the precise functions of which are still disputed |
| 17878236 | We show that upon several types of stress, endogenous PML proteins form nucleolar caps and eventually engulf nucleolar components |
| 17878236 | Only two specific PML splice variants (PML-I and PML-IV) are efficiently targeted to the nucleolus and the abundant PML-I isoform is required for the targeting of endogenous PML proteins to this organelle |
| 17878236 | Furthermore, spontaneous or oncogene retrieval-induced senescence is associated with the formation of very large PML nuclear bodies that initially contain nucleolar components |
| 17878236 | Later, poly-ubiquitin conjugates are found on the outer shell or within most of these senescence-associated PML bodies |
| 17878236 | Thus, unexpectedly, the scarcely studied PML-I isoform links PML bodies, nucleolus, senescence and proteolysis |
| 17643369 | Formation of SAHF is driven by a complex of histone chaperones, HIRA and ASF1a, and depends upon prior localization of HIRA to PML nuclear bodies |
| 17643369 | Repression of Wnt2 occurs early in senescence and independently of the pRB and p53 tumor suppressor proteins and drives relocalization of HIRA to PML bodies, formation of SAHF and senescence, likely through GSK3beta-mediated phosphorylation of HIRA |
| 17428679 | PML protein association with specific nucleolar structures differs in normal, tumor and senescent human cells |
| 17428679 | Promyelocytic leukemia protein (PML), a tumor suppressor, forms in most human cell types discrete multiprotein complexes termed PML nuclear bodies |
| 17428679 | Here, we have used indirect immunofluorescence and confocal microscopy to describe various forms of a novel nuclear PML compartment associated with nucleoli that is found under growth-permitting conditions in human mesenchymal stem cells (hMSC) and skin fibroblasts but not in several immortal cell lines with defects in the p53 and pRb pathways |
| 17428679 | In addition, we found that shut-off of rRNA synthesis induced by actinomycin D causes PML translocation to the surface of segregated nucleoli |
| 17428679 | Intriguingly, treatment causing premature senescence restores PML binding to nucleoli-derived structures and to the surface of segregated nucleoli in HeLa cells |
| 17428679 | These findings indicate that PML may be involved in nucleolar functions of normal non-transformed or senescent cells |
| 17428679 | The absence of nucleolar PML compartment in rapidly growing tumor-derived cells suggests that PML association with the nucleolus might be important for cell-cycle regulation |
| 17242198 | One of the earliest steps in the senescence program is translocation of a histone chaperone, HIRA, into promyelocytic leukemia (PML) nuclear bodies |
| 17242198 | Here, we show that HIRA's translocation to PML bodies occurs in response to all senescence triggers tested |
| 17242198 | Dominant negative HIRA mutants that block HIRA's localization to PML bodies prevent formation of SAHF, as does a PML-RARalpha fusion protein which disrupts PML bodies, directly supporting the idea that localization of HIRA to PML bodies is required for formation of SAHF |
| 17242198 | Significantly, translocation of HIRA to PML bodies occurs in the absence of functional pRB and p53 tumor suppressor pathways |
| 17242198 | However, our evidence indicates that downstream of HIRA's localization to PML bodies, the HIRA/ASF1a pathway cooperates with pRB and p53 to make SAHF, with the HIRA/ASF1a and pRB pathways acting in parallel |
| 17206596 | Promyelocytic leukaemia nuclear domains (PML-NDs) comprise a shell of PML protein and many labile cargo proteins |
| 17206596 | Though the underlying reasons for damage-induced PML alteration remain obscure, it is noteworthy that significant numbers of PML-NDs juxtapose with ionizing radiation-induced foci after IR |
| 16915281 | PML inhibits HIF-1alpha translation and neoangiogenesis through repression of mTOR |
| 16915281 | Loss of the promyelocytic leukaemia (PML) tumour suppressor has been observed in several human cancers |
| 16915281 | The tumour-suppressive function of PML has been attributed to its ability to induce growth arrest, cellular senescence and apoptosis |
| 16915281 | Here we identify PML as a critical inhibitor of neoangiogenesis (the formation of new blood vessels) in vivo, in both ischaemic and neoplastic conditions, through the control of protein translation |
| 16915281 | We demonstrate that in hypoxic conditions PML acts as a negative regulator of the synthesis rate of hypoxia-inducible factor 1alpha (HIF-1alpha) by repressing mammalian target of rapamycin (mTOR) |
| 16915281 | Notably, Pml-/- cells and tumours display higher sensitivity both in vitro and in vivo to growth inhibition by rapamycin, and lack of PML inversely correlates with phosphorylation of ribosomal protein S6 and tumour angiogenesis in mouse and human tumours |
| 16915281 | Thus, our findings identify PML as a novel suppressor of mTOR and neoangiogenesis |
| 16873060 | A CK2-dependent mechanism for degradation of the PML tumor suppressor |
| 16873060 | The PML tumor suppressor controls key pathways for growth suppression, induction of apoptosis, and cellular senescence |
| 16873060 | PML loss occurs frequently in human tumors through unknown posttranslational mechanisms |
| 16873060 | Here we show that CK2 regulates PML protein levels by promoting its ubiquitin-mediated degradation dependent on direct phosphorylation at Ser517 |
| 16873060 | Consequently, PML mutants that are resistant to CK2 phosphorylation display increased tumor-suppressive functions |
| 16873060 | In a faithful mouse model of lung cancer, we demonstrate that Pml inactivation leads to increased tumorigenesis |
| 16873060 | Furthermore, CK2 pharmacological inhibition enhances the PML tumor-suppressive property in vivo |
| 16873060 | Importantly, we found an inverse correlation between CK2 kinase activity and PML protein levels in human lung cancer-derived cell lines and primary specimens |
| 16873060 | These data identify a key posttranslational mechanism that controls PML protein levels and provide therapeutic means toward PML restoration through CK2 inhibition |
| 16778193 | Promyelocytic leukemia (PML) has been implicated in a variety of functions, including control of TP53 function and modulation of cellular senescence |
| 16778193 | Sumolated PML is the organizer of mature PML bodies, recruiting a variety of proteins onto these nuclear domains |
| 16778193 | The PML gene is predicted to encode a variety of protein isoforms |
| 16778193 | We show that all PML isoform proteins are expressed in cell lines or primary cells |
| 16778193 | Stable expression of each isoform, in a pml-null background, yields distinct subcellular localization patterns, suggesting that, like in other RBCC/TRIM proteins, the COOH-terminal domains of PML are involved in interactions with specific cellular components |
| 16778193 | That PML-I contains all conserved exons and is more abundantly expressed than PML-IV suggests that it is a critical contributor to PML function(s) |
| 15657429 | Human papillomavirus oncoprotein E7 targets the promyelocytic leukemia protein and circumvents cellular senescence via the Rb and p53 tumor suppressor pathways |
| 15657429 | Previously, it was shown that the promyelocytic leukemia protein (PML) induces cellular senescence when overexpressed in primary human fibroblasts |
| 15657429 | The mechanism by which the PML IV isoform elicits this irreversible growth arrest is believed to involve activation of the tumor suppressor pathways p21/p53 and p16/Rb; however, a requirement for either pathway has not been demonstrated unequivocally |
| 15657429 | Using different E7 mutant proteins, dominant negative cyclin-dependent kinase 4, and p16 RNA interference, we demonstrate that Rb-related and Rb-independent mechanisms of E7 are necessary for subversion of PML-induced senescence and we identify PML as a novel target for E7 |
| 15657429 | Given the importance of HPV in the pathogenesis of cervical cancer, our results warrant a more detailed analyses of PML in HPV infections |
| 15621527 | These data indicate that HIRA and ASF1a drive formation of macroH2A-containing SAHF and senescence-associated cell cycle exit, via a pathway that appears to depend on flux of heterochromatic proteins through PML bodies |
| 15356634 | Cytoplasmic PML function in TGF-beta signalling |
| 15356634 | The promyelocytic leukaemia (PML) tumour suppressor of acute promyelocytic leukaemia (APL) accumulates in the PML nuclear body, but cytoplasmic PML isoforms of unknown function have also been described |
| 15356634 | Here we show that cytoplasmic Pml is an essential modulator of TGF-beta signalling |
| 15356634 | Expression of cytoplasmic Pml is induced by TGF-beta |
| 15356634 | Furthermore, cytoplasmic PML physically interacts with Smad2/3 and SARA (Smad anchor for receptor activation) and is required for association of Smad2/3 with SARA and for the accumulation of SARA and TGF-beta receptor in the early endosome |
| 15356634 | The PML-RARalpha oncoprotein of APL can antagonize cytoplasmic PML function and APL cells have defects in TGF-beta signalling similar to those observed in Pml-null cells |
| 15356634 | Our findings identify cytoplasmic PML as a critical TGF-beta regulator, and further implicate deregulated TGF-beta signalling in cancer pathogenesis |
| 15111320 | To clarify roles during squamous differentiation (SqD) of endometrial carcinoma (Em Ca) cells, we investigated expression of beta-catenin, as well as cyclin D1, p53, p21WAF1, and PML (promyelocytic leukemia) in 80 cases of Em Ca with SqD areas, in comparison with cell proliferation determined with reference to Ki-67 antigen positivity |
| 15111320 | In clinical cases, nuclear beta-catenin accumulation was more frequent in SqD areas, being positively linked with expression of cyclin D1, p53, and p21WAF1, and inversely with Ki-67 and PML immunoreactivity |
| 15111320 | The Ishikawa cell line, with stable or tetracycline-regulated expression of mutant beta-catenin, showed an increase in expression levels of cyclin D1, p14ARF, p53, and p21WAF1 but not PML, and activation of beta-catenin-TCF4-mediated transcription determined with TOP/FOP constructs |
| 15107834 | HPV E6 proteins interact with specific PML isoforms and allow distinctions to be made between different POD structures |
| 15107834 | We show that both E6 proteins localize within the nucleus in nuclear bodies that are confocal with the promyelocytic leukaemia (PML) protein |
| 15107834 | Using a panel of different PML isoforms, we demonstrate specific co-localization between the E6 proteins and PML isoforms I-IV, but not with PML isoforms V and VI |
| 15107834 | We also demonstrate the interaction between E6 and a subset of PML isoforms in vivo |
| 15107834 | As a consequence of this interaction, the insoluble form of PML IV is destabilized by HPV-18 E6 through a proteasome-dependent pathway |
| 15107834 | These results show separable functions for different PML isoforms that are specifically targeted by the HPV E6 oncoproteins |
| 14712214 | Promyelocytic leukemia protein (PML) is a central component of the senescence response, and is able to trigger the process when overexpressed in human diploid fibroblasts (HDFs) |
| 14712214 | Senescence induced by PML in HDFs is characterized by a modest increase in p53 levels and activity, the accumulation of hypophosphorylated Rb and a reduced expression of E2F-dependent genes |
| 14712214 | We found that the coexpression of E6 and E7 inhibited the growth arrest and senescence induced by PML |
| 14712214 | In addition, these viral oncoproteins blocked the formation of PML bodies and excluded both p53 and Rb from PML bodies |
| 12511612 | Immunostaining of cyan fluorescent protein-labeled SRC-1 (CFP-SRC1)-expressing cells with antibody to promyelocytic leukemia (PML) protein showed significant overlap of the CFP fluorescence with the antibody stain |
| 12511612 | Cotransfection of cells with a plasmid expressing the CFP conjugate of Sp100 (another marker protein for the PML nuclear body) also showed colocalization of the yellow fluorescent protein (YFP)-SRC1 containing nuclear foci with the PML bodies in living cells |
| 12511612 | Analysis of the three-dimensional structure revealed that the PML bodies are round to elliptical in shape with multiple satellite bodies on their surface |
| 12511612 | Activation and nuclear import of CFP-AR by the agonistic ligand 5alpha-dihydrotestosterone, but not by the antagonist casodex, transferred YFP-SRC1 from the PML bodies to an interlacing filamentous structure |
| 12511612 | In a single living cell, agonist-activated AR caused a time-dependent movement of YFP-SRC1 from the PML bodies to this filamentous structure |
| 12511612 | Additionally, coexpression of a constitutively active mutant of AR (AR-deltaligand binding domain) also displaced YFP-SRC1 from the PML bodies to this intranuclear filamentous structure |
| 12511612 | The fluorescence recovery after photobleaching approach was used to examine changes in the kinetics of movement of YFP-SRC1 during its mobilization from the PML bodies to the intranuclear filamentous structure by the agonist-activated AR |
| 12511612 | Results of the relative half-times (t(1/2)) of replacement of YFP-SRC1 within the photobleached region of a single PML body from its surrounding nuclear space supported the conclusion that SRC-1 is actively transported from the PML bodies to the intranuclear filamentous structure by the ligand-activated AR |
| 12511612 | The PML bodies have been implicated as a cross-road for multiple regulatory pathways that control cell proliferation, cellular senescence, and apoptosis |
| 12357343 | PML a target of translocations in APL is a regulator of cellular senescence |
| 12357343 | PML is the most frequent fusion partner of the RARalpha in the specific translocations associated with acute promyelocytic leukemia (APL) |
| 12357343 | Recently, PML has been identified as a regulator of replicative senescence and the premature senescence that occurs in response to oncogenic ras |
| 12006491 | Here, we show that SIRT1, the human Sir2 homolog, is recruited to the promyelocytic leukemia protein (PML) nuclear bodies of mammalian cells upon overexpression of either PML or oncogenic Ras (Ha-rasV12) |
| 12006491 | SIRT1 binds and deacetylates p53, a component of PML nuclear bodies, and it can repress p53-mediated transactivation |
| 12006491 | Moreover, we show that SIRT1 and p53 co-localize in nuclear bodies upon PML upregulation |
| 10910364 | PML regulates p53 acetylation and premature senescence induced by oncogenic Ras |
| 10910364 | Here we report that the tumour suppressor PML regulates the p53 response to oncogenic signals |
| 10910364 | We found that oncogenic Ras upregulates PML expression, and overexpression of PML induces senescence in a p53-dependent manner |
| 10910364 | Lastly, Ras-induced p53 acetylation, p53-CBP complex stabilization and senescence are lost in PML-/- fibroblasts |
| 10910364 | Our data establish a link between PML and p53 and indicate that integrity of the PML bodies is required for p53 acetylation and senescence upon oncogene expression |
| 9213441 | The disruption of the normal function and nuclear localization of the promyelocytic leukemia-associated protein (PML) may play a major role in the pathogenesis of acute promyelocytic leukemia |
| 9213441 | PML, which is concentrated in nuclear bodies (PML bodies), has been shown to have growth- and transformation-suppressive properties |
| 9213441 | In this study, we have examined the intranuclear distribution of PML in a conditionally immortalized human cell line (IDH4) in which both proliferation and immortalization are dependent on the presence of SV40-encoded large T-antigen (SV40T) |
| 9213441 | This is accompanied by a redistribution of PML in most cells from the usual pattern containing only spherical bodies to a pattern, containing large doughnut-like or fiber-like structures in addition to the spherical bodies |
| 9213441 | Moreover, we find that there is a similar change in the PML pattern between young and senescent or serum-starved young IMR90 human fibroblasts, from which IDH4 cells are derived |
| 9213441 | However, fewer serum-starved cells contain large PML bodies than senescent cells |
| 9213441 | Using three-dimensional fluorescence digital imaging microscopy, we have found that the apparently doughnut-like PML structures have a cylindrical or egg-shaped form and that PML is concentrated to the outer shell of the structure |
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